title: As an independent prognostic factor, FAT10 promotes hepatitis B virus-related hepatocellular carcinoma progression via Akt/GSK3β pathway.
abstract: FAT10 is an oncogene that is localized at 6q21.3, a region frequently amplified in hepatocellular carcinoma (HCC). Recently, growing attention has been paid to its effect in the initiation of various cancers. However, there has been little research into the influence of FAT10 on the progression and prognosis of HCC, especially in hepatitis B virus (HBV)-related HCC. Here, we aimed at investigating clincopathological significance of FAT10 in HBV-related HCC and its underlying mechanisms. Based on the analysis of FAT10 expression in a reliable and large number of cases with 5-year follow-up, we showed that FAT10 was significantly increased in 260 samples from HBV-related HCC patients, compared with 30 normal tissue, 50 cirrhosis and matched adjacent nontumor tissues. FAT10 expression is correlated with recurrence and poor prognosis in HBV-related HCC. In addition, ectopic expression of FAT10 enhanced cell proliferation, inhibited apoptosis and induced cell cycle progression, whereas silencing FAT10 expression suppressed cell proliferation and induced apoptosis. FAT10 also induced the epithelial-mesenchymal transition (EMT) and promoted invasion of HCC cells. Furthermore, we found Akt/GSK3β pathway contributed to the effects of FAT10 in HCC cells. Blocking the Akt pathway significantly inhibited the actions of FAT10. Taken together, the ubiquitin-like protein FAT10 has a central role in regulating diverse aspects of the pathogenesis of HCC, indicating that it might be a potential therapeutic target.
authors.affiliation: Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: 1] Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China [2] Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: D
authors.initials: D
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: C109184:UBD protein, human; D014452:Ubiquitins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3